First total synthesis of chromanone A,preparation of related compounds and evaluation of their antifungal activity against Candida albicans,a biofilm forming agent |
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| Authors: | Ivn Corts Estefanía Cordisco Teodoro S Kaufman Maximiliano A Sortino Laura A Svetaz Andrea B J Bracca |
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| Institution: | Instituto de Química Rosario (IQUIR, CONICET-UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK Rosario Argentina.; Area Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK Rosario Argentina, |
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| Abstract: | A straightforward and convenient approach for the first total syntheses of chromanone A and a related 7-OMe substituted natural product is reported. These unique C-3 substituted 2-hydroxymethyl chromones were recently isolated as fungal metabolites. Chromanone A was synthesized in 25.3% overall yield from the readily available pyrocatechol, whereas the second natural product was prepared in 39.7% global yield. A small library of chromones, including both natural products and some of their synthetic heterocyclic precursors, was evaluated against Candida albicans ATCC 10231, a biofilm forming agent. It was found that 8-methoxy-3-methyl-4-oxo-4H-chromene-2-carbaldehyde, a partially oxidized form of chromanone A, exhibited a minimum inhibitory concentration of 7.8 μg mL−1 and significantly inhibited the yeast''s virulence factors, including the adherence to buccal epithelial cells and the secretion of phospholipases, as well as the formation of germ tubes and the generation of the hyphal pseudomycelium. In addition, despite the heterocycle exhibiting non-significant inhibition of the formation of the Candida biofilm, it completely inhibited the growth of C. albicans in preformed biofilms at 62.5 μg mL−1.Chromanone A and its 7-OMe analogue were totally synthesized. 2-Formyl chromanone A derivative inhibited C. albicans and its virulence factors. |
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